Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Efficacy and Safety of Grazoprevir (+) Uprifosbuvir (+) Ruzasvir (MK-3682B) (MK-5172 + MK-3682 + MK-8408) Fixed Dose Combination in Chronic HCV Participants Failing Prior Antiviral Treatment (MK-3682-021)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02613403
Recruitment Status : Terminated
First Posted : November 24, 2015
Results First Posted : March 20, 2018
Last Update Posted : July 26, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Hepatitis
Hepatitis C
Digestive System Diseases
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
RNA Virus Infections
Virus Diseases
Interventions Drug: MK-3682B
Drug: Ribavirin
Enrollment 94
Recruitment Details

For study Part A, 94 cirrhotic (C) or non-cirrhotic (NC) participants with chronic hepatitis C virus (HCV) genotype (GT) 1 previously failing a direct-acting antiviral regimen (DAA) were randomized, with 1 participant withdrawing prior to receiving study treatment.

The trial was terminated prior to participant enrollment for study Part B.

Pre-assignment Details  
Arm/Group Title [Part A, Arm 1] Prior SOF/LDV Failure: MK-3682B + RBV [Part A, Arm 2] Prior SOF/LDV Failure: MK-3682B [Part A, Arm 3] Prior GZR/EBR Failure: MK-3682B + RBV [Part A, Arm 4] Prior GZR/EBR Failure: MK-3682B [Part B] Prior DAA (GT1-6) or SOF/PR (GT3) Failure: MK-3682B
Hide Arm/Group Description C or NC HCV GT1 participants previously failing a DAA regimen of sofosbuvir (SOF)/ledipasvir (LDV) receive MK-3682B, a fixed dose combination (FDC) of grazoprevir (GZR; MK-5172 [50 mg]) + uprifosbuvir (UPR; MK-3682 [225 mg]) + ruzasvir (RZR; MK-8408 [30 mg]), administered as 2 tablets once daily in combination with ribavirin (RBV) twice daily for 16 weeks. C or NC HCV GT1 participants previously failing a DAA regimen of SOF/LDV receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily for 24 weeks. C or NC HCV GT1 participants previously failing a DAA regimen of GZR/elbasvir (EBR) (MK-5172/MK-8742) receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily in combination with RBV twice daily for 16 weeks. C or NC HCV GT1 participants previously failing a DAA regimen of GZR/EBR (MK-5172/MK-8742) receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily for 24 weeks. C or NC HCV participants previously failing any all-oral DAA regimen (GT1-6) or SOF/pegylated interferon and ribavirin (PR) regimen (GT 3 only) receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily for 16 weeks.
Period Title: Overall Study
Started 36 36 9 13 0 [1]
Treated 35 36 9 13 0 [1]
Completed 34 35 9 13 0 [1]
Not Completed 2 1 0 0 0
Reason Not Completed
Lost to Follow-up             0             1             0             0             0
Withdrawal by Subject             2             0             0             0             0
[1]
Study terminated prior to participant recruitment for study Part B.
Arm/Group Title [Part A, Arm 1] Prior SOF/LDV Failure: MK-3682B + RBV [Part A, Arm 2] Prior SOF/LDV Failure: MK-3682B [Part A, Arm 3] Prior GZR/EBR Failure: MK-3682B + RBV [Part A, Arm 4] Prior GZR/EBR Failure: MK-3682B Total
Hide Arm/Group Description C or NC HCV GT1 participants previously failing a DAA regimen of SOF/LDV receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily in combination with RBV twice daily for 16 weeks. C or NC HCV GT1 participants previously failing a DAA regimen of SOF/LDV receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily for 24 weeks. C or NC HCV GT1 participants previously failing a DAA regimen of GZR/EBR (MK-5172/MK-8742) receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily in combination with RBV twice daily for 16 weeks. C or NC HCV GT1 participants previously failing a DAA regimen of GZR/EBR (MK-5172/MK-8742) receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily for 24 weeks. Total of all reporting groups
Overall Number of Baseline Participants 35 36 9 13 93
Hide Baseline Analysis Population Description
Includes only randomized participants in Study Part A receiving ≥1 dose of study treatment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 35 participants 36 participants 9 participants 13 participants 93 participants
59.1  (8.4) 58.9  (6.6) 57.3  (8.5) 53.9  (11.0) 58.1  (8.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 35 participants 36 participants 9 participants 13 participants 93 participants
Female
4
  11.4%
2
   5.6%
3
  33.3%
4
  30.8%
13
  14.0%
Male
31
  88.6%
34
  94.4%
6
  66.7%
9
  69.2%
80
  86.0%
1.Primary Outcome
Title Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After The End of Study Therapy (SVR12)
Hide Description The percentage of participants achieving SVR12 was determined, defined as having a plasma HCV ribonucleic acid (RNA) level below the lower limit of quantification (LLOQ) 12 weeks after the end of study therapy. Plasma HCV RNA level was measured using the Roche COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay with a LLOQ of 15 IU/mL.
Time Frame 12 weeks following final dose of study treatment ([MK-3682B + RBV Groups]: Study Week 28; [MK-3682B Groups]: Study Week 36)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in Part A receiving ≥1 dose of study treatment. Part B was terminated prior to participant enrollment and was not included for analysis.
Arm/Group Title [Part A, Arm 1] Prior SOF/LDV Failure: MK-3682B + RBV [Part A, Arm 2] Prior SOF/LDV Failure: MK-3682B [Part A, Arm 3] Prior GZR/EBR Failure: MK-3682B + RBV [Part A, Arm 4] Prior GZR/EBR Failure: MK-3682B
Hide Arm/Group Description:
C or NC HCV GT1 participants previously failing a DAA regimen of SOF/LDV receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily in combination with RBV twice daily for 16 weeks.
C or NC HCV GT1 participants previously failing a DAA regimen of SOF/LDV receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily for 24 weeks.
C or NC HCV GT1 participants previously failing a DAA regimen of GZR/EBR (MK-5172/MK-8742) receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily in combination with RBV twice daily for 16 weeks.
C or NC HCV GT1 participants previously failing a DAA regimen of GZR/EBR (MK-5172/MK-8742) receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily for 24 weeks.
Overall Number of Participants Analyzed 35 36 9 13
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage
97.1
(85.1 to 99.9)
100.0
(90.3 to 100.0)
100.0
(66.4 to 100.0)
100.0
(75.3 to 100.0)
2.Primary Outcome
Title Number of Participants Who Experienced an Adverse Event
Hide Description The number of participants experiencing an adverse event (AE) was assessed. An AE is any unfavorable and unintended medical occurrence, symptom, or disease witnessed in a participant, regardless of whether or not a causal relationship with the study treatment can be demonstrated. Further, any worsening of a preexisting condition that is temporally associated with the use of the study treatment is also considered an AE.
Time Frame Up to 2 weeks following cessation of study treatment ([MK-3682B + RBV Groups]: Up to Week 18; [MK-3682B Groups]: Up to Week 26)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in Part A receiving ≥1 dose of study treatment. Part B was terminated prior to participant enrollment and was not included for analysis.
Arm/Group Title [Part A, Arm 1] Prior SOF/LDV Failure: MK-3682B + RBV [Part A, Arm 2] Prior SOF/LDV Failure: MK-3682B [Part A, Arm 3] Prior GZR/EBR Failure: MK-3682B + RBV [Part A, Arm 4] Prior GZR/EBR Failure: MK-3682B
Hide Arm/Group Description:
C or NC HCV GT1 participants previously failing a DAA regimen of SOF/LDV receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily in combination with RBV twice daily for 16 weeks.
C or NC HCV GT1 participants previously failing a DAA regimen of SOF/LDV receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily for 24 weeks.
C or NC HCV GT1 participants previously failing a DAA regimen of GZR/EBR (MK-5172/MK-8742) receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily in combination with RBV twice daily for 16 weeks.
C or NC HCV GT1 participants previously failing a DAA regimen of GZR/EBR (MK-5172/MK-8742) receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily for 24 weeks.
Overall Number of Participants Analyzed 35 36 9 13
Measure Type: Count of Participants
Unit of Measure: Participants
31
  88.6%
27
  75.0%
9
 100.0%
12
  92.3%
3.Primary Outcome
Title Number of Participants Who Discontinued Study Drug Due to an Adverse Event
Hide Description The number of participants discontinuing study drug due to an AE was assessed.
Time Frame Up to 2 weeks following cessation of study treatment ([MK-3682B + RBV Groups]: Up to Week 18; [MK-3682B Groups]: Up to Week 26)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in Part A receiving ≥1 dose of study treatment. Part B was terminated prior to participant enrollment and was not included for analysis.
Arm/Group Title [Part A, Arm 1] Prior SOF/LDV Failure: MK-3682B + RBV [Part A, Arm 2] Prior SOF/LDV Failure: MK-3682B [Part A, Arm 3] Prior GZR/EBR Failure: MK-3682B + RBV [Part A, Arm 4] Prior GZR/EBR Failure: MK-3682B
Hide Arm/Group Description:
C or NC HCV GT1 participants previously failing a DAA regimen of SOF/LDV receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily in combination with RBV twice daily for 16 weeks.
C or NC HCV GT1 participants previously failing a DAA regimen of SOF/LDV receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily for 24 weeks.
C or NC HCV GT1 participants previously failing a DAA regimen of GZR/EBR (MK-5172/MK-8742) receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily in combination with RBV twice daily for 16 weeks.
C or NC HCV GT1 participants previously failing a DAA regimen of GZR/EBR (MK-5172/MK-8742) receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily for 24 weeks.
Overall Number of Participants Analyzed 35 36 9 13
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
4.Primary Outcome
Title Number of Participants Who Experienced a Serious Adverse Event
Hide Description The number of participants experiencing a serious adverse event (SAE) was assessed. An SAE is an adverse event that: results in death; is life threatening; results in persistent or significant disability or incapacity; results in or prolongs a hospitalization; is a congenital anomaly or birth defect; is a cancer; or may jeopardize the participant, potentially require medical or surgical intervention.
Time Frame Up to 2 weeks following cessation of study treatment ([MK-3682B + RBV Groups]: Up to Week 18; [MK-3682B Groups]: Up to Week 26)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in Part A receiving ≥1 dose of study treatment. Part B was terminated prior to participant enrollment and was not included for analysis.
Arm/Group Title [Part A, Arm 1] Prior SOF/LDV Failure: MK-3682B + RBV [Part A, Arm 2] Prior SOF/LDV Failure: MK-3682B [Part A, Arm 3] Prior GZR/EBR Failure: MK-3682B + RBV [Part A, Arm 4] Prior GZR/EBR Failure: MK-3682B
Hide Arm/Group Description:
C or NC HCV GT1 participants previously failing a DAA regimen of SOF/LDV receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily in combination with RBV twice daily for 16 weeks.
C or NC HCV GT1 participants previously failing a DAA regimen of SOF/LDV receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily for 24 weeks.
C or NC HCV GT1 participants previously failing a DAA regimen of GZR/EBR (MK-5172/MK-8742) receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily in combination with RBV twice daily for 16 weeks.
C or NC HCV GT1 participants previously failing a DAA regimen of GZR/EBR (MK-5172/MK-8742) receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily for 24 weeks.
Overall Number of Participants Analyzed 35 36 9 13
Measure Type: Count of Participants
Unit of Measure: Participants
3
   8.6%
4
  11.1%
0
   0.0%
1
   7.7%
5.Primary Outcome
Title Number of Participants Who Experienced a Drug-Related Adverse Event
Hide Description The number of participants experiencing a drug-related AE was assessed. A drug-related AE was an AE thought to be possibly, probably, or definitely related to the study drug as determined by the investigator.
Time Frame Up to 2 weeks following cessation of study treatment ([MK-3682B + RBV Groups]: Up to Week 18; [MK-3682B Groups]: Up to Week 26)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in Part A receiving ≥1 dose of study treatment. Part B was terminated prior to participant enrollment and was not included for analysis.
Arm/Group Title [Part A, Arm 1] Prior SOF/LDV Failure: MK-3682B + RBV [Part A, Arm 2] Prior SOF/LDV Failure: MK-3682B [Part A, Arm 3] Prior GZR/EBR Failure: MK-3682B + RBV [Part A, Arm 4] Prior GZR/EBR Failure: MK-3682B
Hide Arm/Group Description:
C or NC HCV GT1 participants previously failing a DAA regimen of SOF/LDV receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily in combination with RBV twice daily for 16 weeks.
C or NC HCV GT1 participants previously failing a DAA regimen of SOF/LDV receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily for 24 weeks.
C or NC HCV GT1 participants previously failing a DAA regimen of GZR/EBR (MK-5172/MK-8742) receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily in combination with RBV twice daily for 16 weeks.
C or NC HCV GT1 participants previously failing a DAA regimen of GZR/EBR (MK-5172/MK-8742) receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily for 24 weeks.
Overall Number of Participants Analyzed 35 36 9 13
Measure Type: Count of Participants
Unit of Measure: Participants
23
  65.7%
18
  50.0%
9
 100.0%
5
  38.5%
6.Primary Outcome
Title Number of Participants Who Experienced a Serious and Drug-Related Adverse Event
Hide Description The number of participants experiencing a serious and drug-related AE was assessed.
Time Frame Up to 2 weeks following cessation of study treatment ([MK-3682B + RBV Groups]: Up to Week 18; [MK-3682B Groups]: Up to Week 26)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in Part A receiving ≥1 dose of study treatment. Part B was terminated prior to participant enrollment and was not included for analysis.
Arm/Group Title [Part A, Arm 1] Prior SOF/LDV Failure: MK-3682B + RBV [Part A, Arm 2] Prior SOF/LDV Failure: MK-3682B [Part A, Arm 3] Prior GZR/EBR Failure: MK-3682B + RBV [Part A, Arm 4] Prior GZR/EBR Failure: MK-3682B
Hide Arm/Group Description:
C or NC HCV GT1 participants previously failing a DAA regimen of SOF/LDV receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily in combination with RBV twice daily for 16 weeks.
C or NC HCV GT1 participants previously failing a DAA regimen of SOF/LDV receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily for 24 weeks.
C or NC HCV GT1 participants previously failing a DAA regimen of GZR/EBR (MK-5172/MK-8742) receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily in combination with RBV twice daily for 16 weeks.
C or NC HCV GT1 participants previously failing a DAA regimen of GZR/EBR (MK-5172/MK-8742) receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily for 24 weeks.
Overall Number of Participants Analyzed 35 36 9 13
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
7.Primary Outcome
Title Number of Participants Who Experienced an Accidental or Intentional Overdose Without Adverse Effect
Hide Description The number of participants experiencing an accidental or intentional overdose without adverse effect was determined. Per study protocol, any occurrence of a participant receiving either MK-3682B or RBV at any dose higher than prescribed was considered an overdose. If this definition of overdose was met without any associated clinical symptoms or abnormal laboratory results, this occurrence of overdose was reported as an accidental or intentional overdose without adverse effect.
Time Frame Up to 2 weeks following cessation of study treatment ([MK-3682B + RBV Groups]: Up to Week 18; [MK-3682B Groups]: Up to Week 26)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in Part A receiving ≥1 dose of study treatment. Part B was terminated prior to participant enrollment and was not included for analysis.
Arm/Group Title [Part A, Arm 1] Prior SOF/LDV Failure: MK-3682B + RBV [Part A, Arm 2] Prior SOF/LDV Failure: MK-3682B [Part A, Arm 3] Prior GZR/EBR Failure: MK-3682B + RBV [Part A, Arm 4] Prior GZR/EBR Failure: MK-3682B
Hide Arm/Group Description:
C or NC HCV GT1 participants previously failing a DAA regimen of SOF/LDV receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily in combination with RBV twice daily for 16 weeks.
C or NC HCV GT1 participants previously failing a DAA regimen of SOF/LDV receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily for 24 weeks.
C or NC HCV GT1 participants previously failing a DAA regimen of GZR/EBR (MK-5172/MK-8742) receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily in combination with RBV twice daily for 16 weeks.
C or NC HCV GT1 participants previously failing a DAA regimen of GZR/EBR (MK-5172/MK-8742) receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily for 24 weeks.
Overall Number of Participants Analyzed 35 36 9 13
Measure Type: Count of Participants
Unit of Measure: Participants
Overdose
1
   2.9%
3
   8.3%
2
  22.2%
1
   7.7%
8.Primary Outcome
Title Number of Participants Who Experienced a Non-Overdose Event of Clinical Interest
Hide Description The number of participants experiencing a non-overdose event of clinical interest (ECI) was determined. Non-overdose ECIs, assessed from initiation of study therapy through 14 days following study treatment cessation, included the following: 1) aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >500 IU/L; or 2) AST or ALT >3x nadir value and >3X upper limit normal (ULN).
Time Frame Up to 2 weeks following cessation of study treatment ([MK-3682B + RBV Groups]: Up to Week 18; [MK-3682B Groups]: Up to Week 26)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in Part A receiving ≥1 dose of study treatment. Part B was terminated prior to participant enrollment and was not included for analysis.
Arm/Group Title [Part A, Arm 1] Prior SOF/LDV Failure: MK-3682B + RBV [Part A, Arm 2] Prior SOF/LDV Failure: MK-3682B [Part A, Arm 3] Prior GZR/EBR Failure: MK-3682B + RBV [Part A, Arm 4] Prior GZR/EBR Failure: MK-3682B
Hide Arm/Group Description:
C or NC HCV GT1 participants previously failing a DAA regimen of SOF/LDV receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily in combination with RBV twice daily for 16 weeks.
C or NC HCV GT1 participants previously failing a DAA regimen of SOF/LDV receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily for 24 weeks.
C or NC HCV GT1 participants previously failing a DAA regimen of GZR/EBR (MK-5172/MK-8742) receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily in combination with RBV twice daily for 16 weeks.
C or NC HCV GT1 participants previously failing a DAA regimen of GZR/EBR (MK-5172/MK-8742) receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily for 24 weeks.
Overall Number of Participants Analyzed 35 36 9 13
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
1
   2.8%
0
   0.0%
0
   0.0%
9.Primary Outcome
Title Number of Participants Who Experienced AST/ALT >5x Upper Limit Normal (ULN)
Hide Description The number of participants experiencing AST / ALT >5 times ULN from study week 4 until 2 weeks following completion of study therapy was determined.
Time Frame From Study Week 4 up to 2 weeks following cessation of study treatment ([MK-3682B + RBV Groups]: Up to Week 18; [MK-3682B Groups]: Up to Week 26)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in Part A receiving ≥1 dose of study treatment with ≥1 AST/ALT measurement subsequent to study week 4. One participant with prior SOF/LDV failure receiving MK-3682B + RBV withdrew from study before study week 4 and was excluded from analysis. Part B terminated prior to enrollment and was not included for analysis.
Arm/Group Title [Part A, Arm 1] Prior SOF/LDV Failure: MK-3682B + RBV [Part A, Arm 2] Prior SOF/LDV Failure: MK-3682B [Part A, Arm 3] Prior GZR/EBR Failure: MK-3682B + RBV [Part A, Arm 4] Prior GZR/EBR Failure: MK-3682B
Hide Arm/Group Description:
C or NC HCV GT1 participants previously failing a DAA regimen of SOF/LDV receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily in combination with RBV twice daily for 16 weeks.
C or NC HCV GT1 participants previously failing a DAA regimen of SOF/LDV receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily for 24 weeks.
C or NC HCV GT1 participants previously failing a DAA regimen of GZR/EBR (MK-5172/MK-8742) receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily in combination with RBV twice daily for 16 weeks.
C or NC HCV GT1 participants previously failing a DAA regimen of GZR/EBR (MK-5172/MK-8742) receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily for 24 weeks.
Overall Number of Participants Analyzed 34 36 9 13
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Time Frame Up to 2 weeks following cessation of study treatment ([MK-3682B + RBV Groups]: Up to Week 18; [MK-3682B Groups]: Up to Week 26)
Adverse Event Reporting Description Includes only randomized participants in Study Part A receiving ≥1 dose of study treatment. The trial was terminated prior to participant enrollment for study Part B.
 
Arm/Group Title [Part A, Arm 1] Prior SOF/LDV Failure: MK-3682B + RBV [Part A, Arm 2] Prior SOF/LDV Failure: MK-3682B [Part A, Arm 3] Prior GZR/EBR Failure: MK-3682B + RBV [Part A, Arm 4] Prior GZR/EBR Failure: MK-3682B
Hide Arm/Group Description C or NC HCV GT1 participants previously failing a DAA regimen of SOF/LDV receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily in combination with RBV twice daily for 16 weeks. C or NC HCV GT1 participants previously failing a DAA regimen of SOF/LDV receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily for 24 weeks. C or NC HCV GT1 participants previously failing a DAA regimen of GZR/EBR (MK-5172/MK-8742) receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily in combination with RBV twice daily for 16 weeks. C or NC HCV GT1 participants previously failing a DAA regimen of GZR/EBR (MK-5172/MK-8742) receive MK-3682B, an FDC of GZR (MK-5172 [50 mg]) + UPR (MK-3682 [225 mg]) + RZR (MK-8408 [30 mg]), administered as 2 tablets once daily for 24 weeks.
All-Cause Mortality
[Part A, Arm 1] Prior SOF/LDV Failure: MK-3682B + RBV [Part A, Arm 2] Prior SOF/LDV Failure: MK-3682B [Part A, Arm 3] Prior GZR/EBR Failure: MK-3682B + RBV [Part A, Arm 4] Prior GZR/EBR Failure: MK-3682B
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/35 (0.00%)      0/36 (0.00%)      0/9 (0.00%)      0/13 (0.00%)    
Hide Serious Adverse Events
[Part A, Arm 1] Prior SOF/LDV Failure: MK-3682B + RBV [Part A, Arm 2] Prior SOF/LDV Failure: MK-3682B [Part A, Arm 3] Prior GZR/EBR Failure: MK-3682B + RBV [Part A, Arm 4] Prior GZR/EBR Failure: MK-3682B
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/35 (8.57%)      4/36 (11.11%)      0/9 (0.00%)      1/13 (7.69%)    
Gastrointestinal disorders         
Pancreatitis  1  0/35 (0.00%)  0 1/36 (2.78%)  1 0/9 (0.00%)  0 0/13 (0.00%)  0
General disorders         
Chest pain  1  0/35 (0.00%)  0 1/36 (2.78%)  1 0/9 (0.00%)  0 0/13 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Bone cyst  1  0/35 (0.00%)  0 0/36 (0.00%)  0 0/9 (0.00%)  0 1/13 (7.69%)  1
Intervertebral disc protrusion  1  0/35 (0.00%)  0 1/36 (2.78%)  1 0/9 (0.00%)  0 0/13 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Hepatocellular carcinoma  1  1/35 (2.86%)  1 1/36 (2.78%)  1 0/9 (0.00%)  0 0/13 (0.00%)  0
Nervous system disorders         
Hydrocephalus  1  1/35 (2.86%)  1 0/36 (0.00%)  0 0/9 (0.00%)  0 0/13 (0.00%)  0
Vascular disorders         
Deep vein thrombosis  1  1/35 (2.86%)  1 0/36 (0.00%)  0 0/9 (0.00%)  0 0/13 (0.00%)  0
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
[Part A, Arm 1] Prior SOF/LDV Failure: MK-3682B + RBV [Part A, Arm 2] Prior SOF/LDV Failure: MK-3682B [Part A, Arm 3] Prior GZR/EBR Failure: MK-3682B + RBV [Part A, Arm 4] Prior GZR/EBR Failure: MK-3682B
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   29/35 (82.86%)      25/36 (69.44%)      9/9 (100.00%)      12/13 (92.31%)    
Blood and lymphatic system disorders         
Anaemia  1  3/35 (8.57%)  3 0/36 (0.00%)  0 1/9 (11.11%)  1 0/13 (0.00%)  0
Cardiac disorders         
Palpitations  1  1/35 (2.86%)  1 0/36 (0.00%)  0 1/9 (11.11%)  2 0/13 (0.00%)  0
Tachycardia  1  1/35 (2.86%)  1 0/36 (0.00%)  0 0/9 (0.00%)  0 1/13 (7.69%)  1
Ear and labyrinth disorders         
Ear pain  1  2/35 (5.71%)  2 0/36 (0.00%)  0 0/9 (0.00%)  0 0/13 (0.00%)  0
Eye disorders         
Vision blurred  1  0/35 (0.00%)  0 1/36 (2.78%)  1 1/9 (11.11%)  1 1/13 (7.69%)  1
Gastrointestinal disorders         
Abdominal pain  1  0/35 (0.00%)  0 0/36 (0.00%)  0 1/9 (11.11%)  1 1/13 (7.69%)  1
Abdominal pain upper  1  1/35 (2.86%)  1 1/36 (2.78%)  1 1/9 (11.11%)  1 2/13 (15.38%)  2
Constipation  1  0/35 (0.00%)  0 3/36 (8.33%)  3 0/9 (0.00%)  0 0/13 (0.00%)  0
Diarrhoea  1  2/35 (5.71%)  3 3/36 (8.33%)  4 2/9 (22.22%)  2 2/13 (15.38%)  3
Dry mouth  1  3/35 (8.57%)  3 0/36 (0.00%)  0 0/9 (0.00%)  0 0/13 (0.00%)  0
Dyspepsia  1  2/35 (5.71%)  2 0/36 (0.00%)  0 1/9 (11.11%)  1 0/13 (0.00%)  0
Flatulence  1  2/35 (5.71%)  2 1/36 (2.78%)  1 1/9 (11.11%)  1 0/13 (0.00%)  0
Gastritis  1  1/35 (2.86%)  1 0/36 (0.00%)  0 1/9 (11.11%)  1 0/13 (0.00%)  0
Large intestine polyp  1  2/35 (5.71%)  2 0/36 (0.00%)  0 0/9 (0.00%)  0 0/13 (0.00%)  0
Nausea  1  1/35 (2.86%)  1 2/36 (5.56%)  2 0/9 (0.00%)  0 0/13 (0.00%)  0
Proctitis  1  0/35 (0.00%)  0 0/36 (0.00%)  0 1/9 (11.11%)  1 0/13 (0.00%)  0
Rectal haemorrhage  1  2/35 (5.71%)  2 0/36 (0.00%)  0 0/9 (0.00%)  0 0/13 (0.00%)  0
Toothache  1  1/35 (2.86%)  1 2/36 (5.56%)  2 0/9 (0.00%)  0 0/13 (0.00%)  0
Vomiting  1  2/35 (5.71%)  2 2/36 (5.56%)  2 0/9 (0.00%)  0 0/13 (0.00%)  0
General disorders         
Asthenia  1  0/35 (0.00%)  0 1/36 (2.78%)  1 0/9 (0.00%)  0 1/13 (7.69%)  1
Fatigue  1  15/35 (42.86%)  17 7/36 (19.44%)  7 6/9 (66.67%)  10 5/13 (38.46%)  5
Influenza like illness  1  0/35 (0.00%)  0 1/36 (2.78%)  1 1/9 (11.11%)  1 0/13 (0.00%)  0
Malaise  1  0/35 (0.00%)  0 0/36 (0.00%)  0 1/9 (11.11%)  1 0/13 (0.00%)  0
Oedema peripheral  1  1/35 (2.86%)  1 3/36 (8.33%)  3 0/9 (0.00%)  0 0/13 (0.00%)  0
Pyrexia  1  0/35 (0.00%)  0 2/36 (5.56%)  2 1/9 (11.11%)  1 0/13 (0.00%)  0
Infections and infestations         
Conjunctivitis  1  0/35 (0.00%)  0 0/36 (0.00%)  0 1/9 (11.11%)  1 0/13 (0.00%)  0
Cystitis  1  0/35 (0.00%)  0 0/36 (0.00%)  0 0/9 (0.00%)  0 1/13 (7.69%)  2
Lower respiratory tract infection  1  0/35 (0.00%)  0 0/36 (0.00%)  0 0/9 (0.00%)  0 1/13 (7.69%)  1
Nasopharyngitis  1  2/35 (5.71%)  2 3/36 (8.33%)  4 0/9 (0.00%)  0 1/13 (7.69%)  1
Sinusitis  1  1/35 (2.86%)  1 1/36 (2.78%)  3 0/9 (0.00%)  0 1/13 (7.69%)  1
Tooth abscess  1  0/35 (0.00%)  0 1/36 (2.78%)  2 1/9 (11.11%)  1 0/13 (0.00%)  0
Urinary tract infection  1  1/35 (2.86%)  1 2/36 (5.56%)  2 0/9 (0.00%)  0 1/13 (7.69%)  1
Viral upper respiratory tract infection  1  0/35 (0.00%)  0 0/36 (0.00%)  0 0/9 (0.00%)  0 1/13 (7.69%)  1
Injury, poisoning and procedural complications         
Accidental overdose  1  1/35 (2.86%)  1 3/36 (8.33%)  3 2/9 (22.22%)  2 1/13 (7.69%)  1
Subcutaneous haematoma  1  0/35 (0.00%)  0 0/36 (0.00%)  0 0/9 (0.00%)  0 1/13 (7.69%)  1
Wound  1  0/35 (0.00%)  0 0/36 (0.00%)  0 0/9 (0.00%)  0 1/13 (7.69%)  1
Investigations         
Haemoglobin decreased  1  3/35 (8.57%)  3 0/36 (0.00%)  0 0/9 (0.00%)  0 0/13 (0.00%)  0
Metabolism and nutrition disorders         
Decreased appetite  1  0/35 (0.00%)  0 0/36 (0.00%)  0 3/9 (33.33%)  3 0/13 (0.00%)  0
Diabetes mellitus  1  0/35 (0.00%)  0 0/36 (0.00%)  0 0/9 (0.00%)  0 1/13 (7.69%)  1
Hyperlipidaemia  1  0/35 (0.00%)  0 0/36 (0.00%)  0 0/9 (0.00%)  0 1/13 (7.69%)  1
Musculoskeletal and connective tissue disorders         
Arthralgia  1  0/35 (0.00%)  0 1/36 (2.78%)  1 0/9 (0.00%)  0 1/13 (7.69%)  1
Arthritis  1  2/35 (5.71%)  2 0/36 (0.00%)  0 0/9 (0.00%)  0 0/13 (0.00%)  0
Muscle spasms  1  2/35 (5.71%)  2 2/36 (5.56%)  2 1/9 (11.11%)  1 0/13 (0.00%)  0
Nervous system disorders         
Dizziness  1  1/35 (2.86%)  1 2/36 (5.56%)  2 3/9 (33.33%)  3 0/13 (0.00%)  0
Dysgeusia  1  1/35 (2.86%)  1 0/36 (0.00%)  0 1/9 (11.11%)  1 0/13 (0.00%)  0
Headache  1  1/35 (2.86%)  1 5/36 (13.89%)  5 5/9 (55.56%)  7 1/13 (7.69%)  1
Lethargy  1  0/35 (0.00%)  0 0/36 (0.00%)  0 1/9 (11.11%)  1 0/13 (0.00%)  0
Sciatica  1  1/35 (2.86%)  1 0/36 (0.00%)  0 0/9 (0.00%)  0 1/13 (7.69%)  1
Syncope  1  0/35 (0.00%)  0 0/36 (0.00%)  0 1/9 (11.11%)  1 0/13 (0.00%)  0
Tremor  1  0/35 (0.00%)  0 0/36 (0.00%)  0 1/9 (11.11%)  1 1/13 (7.69%)  1
Psychiatric disorders         
Anxiety  1  1/35 (2.86%)  1 0/36 (0.00%)  0 0/9 (0.00%)  0 1/13 (7.69%)  1
Emotional disorder  1  0/35 (0.00%)  0 0/36 (0.00%)  0 0/9 (0.00%)  0 1/13 (7.69%)  1
Insomnia  1  3/35 (8.57%)  3 0/36 (0.00%)  0 1/9 (11.11%)  1 0/13 (0.00%)  0
Irritability  1  2/35 (5.71%)  2 1/36 (2.78%)  1 0/9 (0.00%)  0 1/13 (7.69%)  1
Mood altered  1  0/35 (0.00%)  0 0/36 (0.00%)  0 1/9 (11.11%)  1 0/13 (0.00%)  0
Nervousness  1  0/35 (0.00%)  0 0/36 (0.00%)  0 1/9 (11.11%)  1 0/13 (0.00%)  0
Stress  1  0/35 (0.00%)  0 0/36 (0.00%)  0 0/9 (0.00%)  0 1/13 (7.69%)  1
Respiratory, thoracic and mediastinal disorders         
Cough  1  2/35 (5.71%)  2 2/36 (5.56%)  4 1/9 (11.11%)  1 2/13 (15.38%)  2
Dyspnoea  1  2/35 (5.71%)  2 2/36 (5.56%)  2 2/9 (22.22%)  2 0/13 (0.00%)  0
Dyspnoea exertional  1  3/35 (8.57%)  3 0/36 (0.00%)  0 0/9 (0.00%)  0 0/13 (0.00%)  0
Epistaxis  1  0/35 (0.00%)  0 0/36 (0.00%)  0 1/9 (11.11%)  1 0/13 (0.00%)  0
Respiratory tract congestion  1  0/35 (0.00%)  0 0/36 (0.00%)  0 0/9 (0.00%)  0 1/13 (7.69%)  1
Rhinitis allergic  1  0/35 (0.00%)  0 0/36 (0.00%)  0 0/9 (0.00%)  0 1/13 (7.69%)  1
Skin and subcutaneous tissue disorders         
Dry skin  1  0/35 (0.00%)  0 0/36 (0.00%)  0 1/9 (11.11%)  1 0/13 (0.00%)  0
Pruritus  1  4/35 (11.43%)  6 0/36 (0.00%)  0 1/9 (11.11%)  1 0/13 (0.00%)  0
Rash  1  6/35 (17.14%)  8 2/36 (5.56%)  2 0/9 (0.00%)  0 0/13 (0.00%)  0
Skin lesion  1  0/35 (0.00%)  0 0/36 (0.00%)  0 1/9 (11.11%)  1 0/13 (0.00%)  0
Vascular disorders         
Hypertension  1  0/35 (0.00%)  0 1/36 (2.78%)  1 0/9 (0.00%)  0 1/13 (7.69%)  1
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02613403    
Other Study ID Numbers: 3682-021
2015-001483-19 ( EudraCT Number )
MK-3682-021 ( Other Identifier: Merck Protocol Number )
First Submitted: November 20, 2015
First Posted: November 24, 2015
Results First Submitted: February 2, 2018
Results First Posted: March 20, 2018
Last Update Posted: July 26, 2019